Marijuana use in the immediate 5-year premorbid period is associated with increased risk of onset of schizophrenia and related psychotic disorders

Objectives: Several studies suggest that adolescent marijuana use predicts earlier age at onset of schizophrenia, which is a crucial prognostic indicator. Yet, many investigations have not adequately established a clear temporal relationship between the use and onset. Methods: We enrolled 247 first-episode psychosis patients from six psychiatric units and collected data on lifetime marijuana/alcohol/tobacco use, and ages at onset of prodrome and psychosis in 210 of these patients. Cox regression (survival analysis) was employed to quantify hazard ratios (HRs) for effects of diverse premorbid use variables on psychosis onset. Results: Escalation of premorbid use in the 5 years prior to onset was highly predictive of an increased risk for onset (e.g., increasing from no use to daily use, HR = 3.6, p < 0.0005). Through the analysis of time-specific measures, we determined that daily use approximately doubled the rate of onset (HR = 2.2, p < 0.0005), even after controlling for simultaneous alcohol/tobacco use. Building on previous studies, we were able to determine that cumulative marijuana exposure was associated with an increased rate of onset of psychosis (p = 0.007), independent of gender and family history, and this is possibly the reason for age at initiation of marijuana use also being associated with rate of onset in this cohort. Conclusions: These data provide evidence of a clear temporal relationship between escalations in use in the five years pre-onset and an increased rate of onset, demonstrate that the strength of the association is similar pre- and post-onset of prodromal symptoms, and determine that early adult use may be just as important as adolescent use in these associations. (C) 2016 Elsevier B.V. All rights reserved.